Early detection

Hispanics/LatinX comprise the largest-growing minority group in the United States (U.S.). They account for 18.5% of the total U.S. population1 and are projected to become the largest group in the U.S. by 2045, surpassing NHW. Despite large national representation in the U.S., data demonstrates that this population faces barriers to healthcare access. These barriers are often due, but not limited to socioeconomic status, lack of health insurance, limited medical literacy, language barriers, structural racism, and perceived discrimination. Studies show that Hispanics/LatinX have the highest uninsured rates compared to any other ethnic/racial group, thus limiting their ability to receive equitable health care. This lack of equitable care often leads to Hispanics/LatinX forgoing or delaying medical care, avoiding screening, placing them at elevated risk of an advanced stage of cancer diagnosis. Unlike NHW, cancer remains the most common cause of death in the Hispanic/LatinX population.

LC is the leading cause of cancer-related death for Hispanic/LatinX men and the second most common cause of death for Hispanic/LatinX women. LC carries a 5-year overall survival rate of less than 20%, mainly due to advance stage at diagnosis. Survival rates are even lower for Hispanics/LatinX (13% vs 17%), who are more likely to be diagnosed at advanced stages of LC than their NHW counterparts (59% vs 52%). To increase the rates of early detection, different organizations have supported the use of LDCT as a screening modality in eligible individuals, after results from the NLST showed a 20% mortality reduction in LC with the use of LDCT for screening. Currently, The U.S. Preventive Services Task Force (USPSTF) recommends annual screening for LC in adults 50–80 years of age with at least a 20-pack year smoking history who are current smokers or have quit within the last 15 years. This criterion was extrapolated from the high-risk features in subjects that participated in the NLST that ultimately led to the LC screening recommendations. Unfortunately, the population in the NLST is not an accurate representation of the U.S population, as 95% of the participants were white and only 1.8% were Hispanics. Additionally, studies have shown that LatinX individuals are less aware of LC screening than NHW, but when informed, they are more LatinX interested in pursuing screening (90.7%) compared with non-LatinX (67%).

Besides tobacco use, having a previous malignancy is a risk factor for LC. HNC survivors are at increased
risk of second primary lung cancer compared to the general population, largely due to their heavy smoking history. Patients with tobacco related HNC have up to a 13% risk of developing second primary LC. Currently, the guidelines recommend performing a 3-month post treatment for subjects with head and neck malignancies treated with curative intent. However, NCCN does not advise performing imaging surveillance beyond 6 months in this patient population, unless there are signs and/or symptoms to suggest cancer recurrence. In reference to LC screening, The NCCN recommends annual screening with LDCT for HNC survivors with a smoking history of 20 pack years or more. However, no prospective studies have been performed to assess the risk of second primary LC in this high-risk population. Of the few studies that have been completed, one study completed a post hoc secondary analysis of the NLST to evaluate the incidence of second primary lung cancer in HNC survivors screened with low dose CT (LDCT) versus chest x-ray (CXR). Out of X participants, 171 HNC survivors had undergone screening. Of these, 90.1% identified as White, 4.1% as Black, and 0% as Hispanic or LatinX and lung cancer was identified in 20 (12%) of the HNC survivors screened. A total of 15% (12/82) and 9% (8/89) of the HNC survivors screened with LDCT and CXR, respectively, were diagnosed with LC. The study found a higher LC incidence in HNC survivors compared to participants without head and neck cancer, with an adjusted rate ratio of 2.54 (95% CI, 1.63-3.95). Additionally, the study found an average smoking history of 80 pack years amongst HNC survivors compared to 48 pack years in the rest of the study population.

The study proposed here will fill an important gap and assess the awareness and eligibility of lung cancer
screening in Hispanic/LatinX HNC survivors via a survey questionnaire and understand the barriers to
screening via qualitative interviews. We will create the first lung cancer screening program tailored for and focused exclusively on Hispanic/LatinX HNC survivors.

Lung cancer is the leading cause of cancer death in the United States, and disproportionate risk is faced in the lesbian, gay, bisexual, trans and queer (LGBTQ) community due to higher smoker rates. Lung cancer screening (LCS) with annual low-dose chest CT has been demonstrated to reduce lung cancer mortality by up to 20% in a subset of high-risk smokers, a benefit that is doubled with sustained smoking cessation. Little is known about LCS in LGBTQ patients; however, in general, this population faces healthcare discrimination and other unique barriers to preventive care. This study will bridge this significant knowledge gap through partnership with an urban LGBTQ community center to tailor and evaluate a smoking cessation and LCS program for the LGBTQ community through a robust mixed-methods approach centered in community-based participatory research. In Aims 1 and 2, we will use a qualitative approach to engage the community and build a tailored cessation and screening navigation program, and in Aim 3 we will pilot the program in single-arm study, evaluating both effectiveness and the implementation outcomes of the program. Results from this study will assist with the development of a sustainable local LGBTQ LCS and smoking cessation program and will be used to inform a larger multicenter trial of the intervention.

Lung cancer remains the leading cause of cancer death worldwide and clinical trials show that annual lung cancer screening with low-dose Computed Tomography can reduce lung cancer-related mortality by 20%. Marginalized populations are disproportionately affected by lung cancer and our prior work has shown that these disparities extend to lung cancer screening; in a national cohort of Veterans we found that Black Veterans, those with mental health disorders and lower income were less likely to adhere to lung cancer screening follow-up recommendations. Currently, little is known about how to optimize lung cancer screening in underserved populations and marginalized populations from diverse backgrounds.

This proposed project focuses on identifying barriers and facilitators to lung cancer screening at the patient, provider, facility and community-levels. We plan to use mixed methods to quantitatively explore factors associated with delayed or lack of adherence to lung cancer screening and then perform in-depth qualitative analysis to identify which factors are critical and modifiable. We will use an implementation strategy mapping tool to select evidence-based strategies best suited to address the identified barriers and develop a tailored implementation plan to improve adherence to lung cancer screening, both overall and among underserved populations, at Baystate Health System. This work is critical in achieving equity in lung cancer screening and improving overall lung cancer mortality among patients.

Background: Provider engagement is key for successful implementation of evidence-based practices. Our prior work reported that providers’ guideline knowledge is strongly correlated to screening practices but other behavioral factors have not yet been measured in lung cancer screening.

Long-term Career Goal: To be a leader in implementation science with expertise in translating evidence-based lung cancer prevention and early detection into clinical practice through mixed-methods research (qualitative and quantitative) and pragmatic trials in the Veterans Affairs (VA). This award will advance the following career goals: To gain experience in: a) measurement science; b) quantitative analysis methods, and to transition to research independence.

Specific Aim: To measure and validate providers’ behavioral factors that influence lung cancer screening implementation.

Methodology: We will adapt the Determinants of Implementation Behavior Questionnaire (DIBQ) for lung cancer screening and leverage ongoing research infrastructure to survey primary care providers at 10 VA medical centers (VAMCs) participating in the Veterans Affairs Partnership to increase Access to Lung Screening (VA-PALS). The adapted questionnaire will be validated using factor analysis and association with prior screening practices. We will assess which behavioral factors are associated with screening using multivariable regression.

Future Directions: The data gathered will be used to design future interventions aimed at increasing provider engagement and measure how provider engagement changes before and after interventions. This proposal will advance the field of implementation science while also leading towards my independence as an implementation researcher.

Lung cancer remains the leading cause of cancer related mortality in the US and globally— responsible for ~1.8 million deaths annually. Randomized trials of low dose CT (LDCT) for lung cancer screening have demonstrated a clear mortality benefit and are recommended by the United States Preventive Services Task Force (USPSTF). However, most individuals currently eligible for screening do not have lung cancer and many at risk populations are not candidates for screening. Additionally, LDCT has a relatively high rate of false positives leading to potentially harmful tests and invasive procedures. Moreover, early experience suggests that LCS outcomes in clinical practice may differ from those observed in randomized trials. Given the concerns with the performance of LDCT, the use of blood and imaging biomarkers to complement the screening process has the potential to enhance its efficacy and effectiveness. Biomarkers could be employed at two different steps of the screening process – as the initial test for cancer screening, to better define the best candidates for screening, or following a positive LDCT scan, to inform lung nodule evaluation and management. While several screening and diagnostic biomarkers have been developed, they have not been formally evaluated in prospective comparative effectiveness trials, nor have they been subjected to cost-effectiveness analyses. More importantly, their impact on lung cancer burden at the population level is still unknown. Our proposed research will inform the following areas of LCS and biomarker discovery: 1) generate a computational framework to estimate and compare the population impact of emerging screening and diagnostic biomarkers, 2) identify the optimal strategy of integrating biomarker tests into LCS, and 3) highlight and identify the characteristics of biomarkers (sensitivity and specificity for histological subtypes, etc.) which are critical for cost-effective biomarker applications.

Lung cancer is the leading cause of cancer-related death in US, and lung adenocarcinoma (LUAD) is the most frequent histology. Early diagnosis is crucial. High-resolution CT has increased the discovery of solitary lung lesions, many of which are benign, whereas some progress to invasive cancer; the identification of novel biomarkers to predict the malignant potential of these lesions is of paramount importance. We found that sodium-dependent glucose transporter 2 (SGLT2) is expressed in human pre-malignant and early-stage LADC, and is required for progression of LUAD. SGLT activity can be measured by PET imaging with methyl-4-[18F] fluorodeoxyglucose (Me4FDG). Importantly, we identified SGLT2 activity in FDG-negative, early-stage lesions in mouse models and in human lung nodules.

Specific aims of the study are: 1. To assess the safety and efficacy of Me4FDG in patients with lung cancer, via a pilot study in 60 patients (30 with pathological diagnosis of LUAD, 30 with a clinical diagnosis of benign nodule); 2. To evaluate the prognostic significance of SGLT2 expression in early lung adenocarcinoma, through SGLT2 staining of 674 samples embedded in tissue microarrays.

The proposed research is likely to introduce a novel diagnostic tool for early diagnosis of lung adenocarcinoma, and further define the prognostic role of SGLT2 in lung cancer. If successful, this pilot trial will open the way for larger clinical studies where we will evaluate the ability of Me4FDG PET to predict the malignant behavior of indeterminate subsolid lung nodules. This will improve the early diagnosis of lung cancer.